Pinopodes: Recent advancements, current perspectives, and future directions

Successful embryo implantation is a complex and highly regulated process involving precise synchronization between the fetal-derived trophoblast cells and maternal uterine luminal epithelium. Multiple endocrine-driven factors are important for controlling the timely receptivity of the uterus, and this complexity underscores implantation failure as a major cause of recurrent infertility associated with assisted reproductive technologies. One particular cellular structure often hypothesized to promote receptivity is the pinopode or uterodome – a hormonally regulated, large cellular protrusion on the uterine epithelial surface. Recent clinical studies associate pinopodes with favorable fertility outcomes in women, and because they are directly linked to an increase in progesterone levels, the potential utility of these hormone-regulated cell biological structures in predicting or improving implantation in a clinical setting holds promise. In this review, we aim to generate interest in pinopodes from the broader cell biology and endocrinology communities, re-examine methodologies in pinopode research, and identify priorities for future investigation of pinopode structure and function in women's reproductive health. Pinopodes are protrusions of the uterine luminal epithelium present during the window of implantation in both rodents and humans, among other species. [Display omitted] •Review of literature regarding the significance of pinopodes in endometrial receptivity and implantation.•Quantitative and qualitative approaches for pinopodes are discussed.•Clinical relevance of pinopodes is revisited.